Implantable medical devices are becoming increasingly common and more complex. Advances in medical device technology have led to smaller and more complex implants that provide a greater standard of living to an increasingly aging population. However, not all of the materials used in medical implants are entirely biocompatible, i.e. the surrounding tissues may become inflamed when in contact with the surface of the implant. Inflammation results from the infiltration of immune cells such as neutrophils and macrophages to the tissue-implant interface as these cells attempt to repair damage that occurs following implantation. Thus, inflammatory responses against implants remains a problem with respect to both tolerance and maintenance of function for a variety of these implants, ranging from cardiovascular devices (e.g. coronary stents) and electrical devices (e.g. pacemakers and glucose sensors to prostheses such as hip joint replacements). Accordingly, there is a need for biocompatible materials which can coat the implant and serve as vehicles for the targeted delivery of drugs to the surrounding tissues.
Existing delivery technologies include the use of poly(lactic-co-glycolic acid) (PLGA) microspheres as drug-eluting particles for suppression of inflammation. The use of fluidic delivery of anti-inflammatories has also been explored. In addition, poly(3,4-ethylenedioxythiophene (PEDOT) has been used in nanotube and planar formats. Unfortunately, each of the delivery systems provide a relatively thick material associated with an implant. For example, the PLGA microspheres are on the order of 200 microns in diameter, while fluidic delivery materials are several microns in thickness. As a result, these materials significantly impact the design parameters of the implants they serve and generate adverse effects on surrounding tissues because they increase the overall dimensions of the implants and preclude non-invasive behaviors.
In addition, all invasive biomedical devices inherently possess the challenge of overcoming three primary obstacles. These concerns are biocompatibility, bio-longevity, and efficacy. Biomedical devices desire to leap these hurdles and be completely biocompatible to reduce the risk of patient complications, but often, current technologies result in new drawbacks. For example, many types of drug-eluting stents serve to reduce clotting of the stent in implant patients, but are associated with increased clinical complication rates. Because recent advances do not optimally address implant biocompatibility, newer, more effective mechanisms are a necessity.
Pioneering drug delivery as a new field for parylene-based applications fills the need for a biocompatible, functionalized membrane capable of slow-releasing drug to a localized region for targeted delivery. Currently, chemotherapeutic drugs are capable of killing cancerous cells, but cannot selectively kill only cancerous cells; they exhibit universal cytotoxicity. A similar issue exists in administering anti-inflammatory compounds; indiscriminately introducing these compounds significantly dilute drug efficacy and weaken the global immune response, which opens a window for infection. Therefore, it is imperative that drugs are delivered in a targeted fashion.
Drug delivery is an important aspect of medicine as an essential mechanism that bridges drug development and treatment. During the past decade, there has been much attention focused on improving control of drug delivery and the advent of newer technologies including tissue scaffolds and drug-eluting stents is evidence of the desire to have more control over how, where, and when pharmaceutical agents are delivered. Nevertheless, it has been a challenge to create a biocompatible coating capable of eluting drug due to several developmental barriers. Such a material would need to be biologically inert and stable, possess anti-inflammatory mechanisms, and pliable for use in a wide variety of applications. With these criteria in mind, the biomedical industry has sought to create a biocompatible coating that does not interfere with device operation, may abate inflammatory responses, and bolster efficacy of the coated mechanism.
An example of such a search led to the creation of the drug-eluting stent. The drug-eluting stent was created to improve stent longevity and minimize clotting on the stent itself to reduce the risk of neointimal hyperplasia, an excessive immune response to bare metal stent implants that results in narrowing of vessels due to clots, and thus medical complications for the patient. By eluting immunosuppressive drugs from the stent, the inflammatory response was lessened near the implant location of the stent, thus inhibiting platelet activation and preventing neointimal hyperplasia. The drug-eluting stent has revolutionized cardiology, but many stents rely on less than ideal materials, or an unsuitable combination of materials.
For example, while the FDA has concluded that drug-eluting stents are safer and more effective than bare metal stents, certain complications may result from using a drug-eluting stent including severe thrombotic (formation of clot inside a blood vessel) events and restenosis (abnormal narrowing of vessels), despite restenosis and thrombosis being some of the very issues drug eluting stents were created to solve. Therefore, while modern stents are a step forward in reaching complete biocompatibility of implanted devices, much of the present technology is not progressive enough, and the search and necessity for a more biocompatible coating continues.